Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence.

BACKGROUND: In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC. MATERIALS AND METHODS: Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease. Patients were randomly assigned (1:1) to pembrolizumab 200 mg Q3W or investigator's choice of standards of care (SOC): methotrexate, docetaxel, or cetuximab. Outcomes included OS, PFS, ORR, and DOR. The data cutoff was May 15, 2017. RESULTS: There were 125 patients (pembrolizumab, 53; SOC, 72) in the recurrent-only subgroup, 204 in the recurrent-metastatic subgroup (pembrolizumab, 108; SOC, 96), and 166 in the metastatic-only subgroup (pembrolizumab, 86; SOC, 80). The hazard ratio (95% CI) for death for pembrolizumab versus SOC was 0.83 (0.55-1.25) in the recurrent-only, 0.78 (0.58-1.06) in the recurrent-metastatic, and 0.74 (0.52-1.05) in the metastatic-only subgroups. PFS was similar between treatment arms in all subgroups. ORR was 22.6% for pembrolizumab versus 16.7% for SOC in the recurrent-only, 10.2% versus 6.3% in the recurrent-metastatic, and 15.1% versus 8.8% in the metastatic-only subgroups. DOR was numerically longer with pembrolizumab in all subgroups. CONCLUSION: Pembrolizumab provided numerically longer OS and durable responses in all subgroups compared with SOC, suggesting that patients with previously treated R/M HNSCC benefit from pembrolizumab regardless of recurrence pattern.

Simultaneous microwave-assisted extraction of bioactive compounds from aged garlic.

In this work, the simultaneous extraction of bioactives (organosulfur compounds, such as S-allyl-L-cysteine (SAC), carbohydrates, such as neokestose and neonystose, and total phenolic compounds) from aged garlic has been optimized for the first time to obtain multifunctional extracts for further application as food ingredients. Analytical methods using liquid chromatography coupled to mass spectrometry (HPLC-MS) and by hydrophilic interaction liquid chromatography with evaporative light scattering detection (HILIC-ELSD) were also previously optimized. High sensitivity (limits of detection between 0.013 and 0.77 µg mL-1) and appropriate repeatability (< 12%) and accuracy (> 92%) for the analysis of bioactives were achieved. After selecting water as the extraction solvent and microwave-assisted extraction (MAE) as the most efficient technique, operation conditions were optimized using a Box-Behnken experimental design (60 min; 120 °C; 0.05 g mL-1; 1 cycle) to maximize the content of bioactives from different aged garlic samples. Regarding organosulfur compounds, only SAC (traces-2.32 mg g-1 dry sample) and cycloalliin (1.23-3.01 mg g-1 dry sample) were detected in all samples, while amino acids such as arginine (0.24-3.45 mg g-1 dry sample) and proline (0.43-3.91 mg g-1 dry sample) were, in general, the most abundant. Bioactive carbohydrates (from trisaccharides to nonasaccharides) were only detected in fresh garlic and aged garlic processed under mild conditions, whereas all garlic extracts showed antioxidant activity. The developed MAE methodology is shown as a successful alternative to other procedures for the simultaneous extraction of aged garlic bioactives intended by the food and nutraceutical industries, among others.

Special Collection: Highlights of Medical, Urban and Veterinary Entomology. Highlights in Medical Entomology, 2021.

Life remained far from normal as we completed the first year of the Covid-19 pandemic and entered a second year. Despite the challenges faced worldwide, together we continue to move the field of Medical Entomology forward. Here, I reflect on parallels between control of Covid-19 and vector-borne disease control, discuss the advantages and caveats of using new genotyping technologies for the study of invasive species, and proceed to highlight papers that were published between 2020 and 2021 with a focus on those related to mosquito surveillance and population genetics of mosquito vectors.

Saliva collection via capillary method may underestimate arboviral transmission by mosquitoes.

BACKGROUND: Arthropod-borne viruses (arboviruses) impose a major health and economic burden on human populations globally, with mosquitoes serving as important vectors. Measuring the ability of a mosquito population to transmit an arbovirus is important in terms of evaluating its public health risk. In the laboratory, a variety of methods are used to estimate arboviral transmission by mosquitoes, including indirect methods involving viral detection from mosquito saliva collected by forced salivation. The accuracy of indirect methods to estimate arbovirus transmission to live animal hosts has not been fully evaluated. METHODS: We compared three commonly used proxies of arboviral transmission, namely, the presence of virus in mosquito legs, in salivary glands (SG) and in saliva collected in capillary tubes using forced salivation, with direct transmission estimates from mosquitoes to suckling mice. We analyzed five vector-virus combinations, including Aedes aegypti infected with chikungunya virus, West Nile virus and Zika virus; Culex quinquefasciatus infected with West Nile virus; and Aedes triseriatus infected with La Crosse virus. RESULTS: Comparatively, the methods of detecting virus infection in mosquito legs and in SG were equally accurate in predicting transmission. Overall, the presence of virus in mosquito legs was a more accurate predictor of transmission than the commonly implemented viral detection method using forced salivation into a capillary tube, and was subject to less technical variation. CONCLUSIONS: These results suggest that, in general, forced salivation methods tend to underestimate virus transmission, and they provide confidence in the use of mosquito leg screens to evaluate the transmission potential of a mosquito population.

Comprehensive diagnosis of parasites in sheep kept under different zootechnical management in a region temperate in Mexico.

Parasites cause losses in animal production. Parasite infection in ruminants has been estimated to be a major problem causing more than 3 billion USD per year, from which 60% corresponds to the sheep industry. Treatment is based on the use of synthetic anthelmintics; however, repeated application or under dosage have resulted in the selection of nematodes resistant to anthelmintics. The objective of the present work was to perform a diagnosis of gastrointestinal parasites in sheep kept under different zootechnical management. Ninety female sheep were used, most of them pregnant. Sampling was performed monthly from December 2015 to June 2016 (flock 5 until April). Fecal samples were collected from the rectum; the McMaster technique was performed, morphological characteristics were observed, oocysts and eggs were counted per gram of feces (opg and epg), frequency and intensity were obtained. Faecal culture was performed for feces that had a positive result, infective larvae were obtained and taxonomically identified. At the end of the study, a dewormer (fenbendazole) was administered and its effect was measured. The frequency of gastrointestinal parasites was 100%. The highest opg was 3,600 (flock 3, March, 2016), the epg for cestodes was 2800 (flock 1, January, 2016) and for gastrointestinal nematodes (GIN) was 25,000 (flock 1, May, 2016); the intensity was variable and it was increased by peripartum. Protists (Eimeria spp), cestodes (Moniezia) and nematodes (Haemonchus, Trichostrongylus, Cooperia, Chabertia ovina. Teladorsagia, Oesophagostomum, Nematodirus and Trichuris ovis) were identified. No previous diagnosis is performed in flocks, and sometimes dewormers are administered, even though resistance to ivermectin and benzimidazole is suspected. Flock management, its feeding system and its conditions were determinant for the observed results; therefore, it is necessary to count with a diagnosis that provides information about the parasitic population and its dynamic, in order to carry out a selective and comprehensive control that has an impact on the animal, human and environmental health.

[Dupilumab-related blepharoconjunctivitis: Recommendations of the CEDRE group. Atopic dermatitis, conjunctivitis and dupilumab: Which management approach?] / Blépharo-conjonctivites sous dupilumab : recommandations du groupe CEDRE. Dermatite atopique, conjonctivites et dupilumab : quelle prise en charge ?

Dupilumab is a recombinant monoclonal IgG4 type antibody which inhibits IL4 and IL13 signaling. It is indicated in moderate to severe atopic dermatitis (AD) in adults and adolescents over 12 years of age. Its side effects include conjunctivitis and blepharoconjunctivitis, affecting between 4.7% and 28% of patients depending on the study. The incidence of conjunctivitis in patients treated with dupilumab for AD appears to be higher than placebo in clinical studies. This increase was not observed in patients treated with dupilumab for asthma or sinonasal polyposis. The risk factors for conjunctivitis in patients with AD are disease severity, pre-existence of conjunctivitis and low concentrations of dupilumab, but the pathophysiology of this disease is poorly understood. A literature search carried out in April and May 2020 showed an increase in the number of publications on the subject, but there are currently no official joint dermatologist-ophthalmologist recommendations for prevention and management. The objective of this article is to provide an overview of the status of this subject, to address the main questions raised by this type of conjunctivitis and to suggest a course of action for starting and continuing treatment with dupilumab in patients with AD, according to the recommendations of the French Ophthalmologist/Dermatologist group CEDRE.

Cutaneous drug-induced lupus erythematosus: Clinical and immunological characteristics and update on new associated drugs.

Cutaneous drug-induced lupus erythematosus (CDILE) is a lupus-like syndrome related to drug exposure which typically resolves after drug discontinuation. It can present as a systemic or a sole cutaneous form and different drugs may be associated with each form. CDILE pharmacoepidemiology is constantly changing. Indeed, older drugs primarily associated with systemic CDILE are no longer prescribed and new drugs associated with either cutaneous or systemic CDILE have emerged. The present study discusses the clinical and laboratory aspects of CDILE and the postulated pathogenesis, and it provides an update on implicated drugs. We performed a literature review to single out the new drugs associated with CDILE in the past decade (January 2010-June 2020). Among 109 drugs reported to induce CDILE in 472 patients, we identified anti-TNFα, proton-pump inhibitors, antineoplastic drugs, and, in particular, checkpoint inhibitors, as emerging drugs in CDILE. Most of the published studies are cases reports or small case series, and further larger studies as well as the development of validated classification criteria are needed to better understand and characterize their implication in CDILE.

SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Literature review of perceptual learning modules in medical education: What can we conclude regarding dermatology?

INTRODUCTION: Visual pattern recognition is important in many different medical fields, particularly in dermatology. Perceptual learning modules (PLM) are software programs developed to enhance visual pattern recognition through the sequential presentation of images that trainee must quickly diagnose. The aim of this literature review was to determine the scope and effectiveness of PLM in medical education. METHODS: We carried out a search of MEDLINE, EMBASE, Web of Science and ERIC from its inception through to July 1, 2017. All articles describing an educational intervention based on perceptual learning in a medical field were included. Two investigators worked independently on study selection and data extraction. RESULTS: Of 191 references selected, 5 studies were included in the final analysis: 3 before-after studies and 2 randomized studies comparing 12 to 236 trainees taking PLM with 12 to 316 trainees not taking PLM. Four studies reported a statistically significant increase in diagnostic accuracy (lower error rate) and fluency (shorter response time) following PLM interventions (dermatology, pathology, echocardiography), with long-term persistence of the effect in three studies. CONCLUSION: PLM is a promising educational tool to teach pattern recognition that may be used in dermatology and other medical fields to improve diagnostic accuracy and rapidity in daily practice.

[What is neutrophilic urticaria?] / Qu'est-ce que l'urticaire neutrophilique ?

Some debate continues to surround the existence of neutrophilic urticaria (NU) as a nosological entity. Certain authors consider NU as a banal form of urticaria since an infiltrate predominantly made up of polynuclear neutrophils (PNN) is seen in certain cases of chronic and acute urticaria. Moreover, it has been stated that the histological appearance of chronic urticaria varies according to the time between appearance of the plaque and the performance of biopsy: the presence of PNN may occur later. According to the literature, there appear to be no specific clinical characteristics associated with the presence of PNN at histology. Most cases exhibit moderate laboratory inflammatory syndrome. Data concerning therapeutic response are contradictory: some studies have shown no significant difference in terms of therapeutic response in relation to banal urticaria, while only one study has demonstrated superior response to dapsone in the case of histologically demonstrated neutrophilic infiltrate. There does not appear to be any disease more frequently associated in the event of NU. In conclusion, the available data concerning NU are insufficient to confirm the existence of this condition. A prospective study comparing routine acute and chronic urticaria biopsies would be extremely useful to better characterise the relationships between cellular infiltrate and therapeutic response.